engleski

Innate immunity to hantaviruses

Hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Monocytes and endothelial cells are considered as the main target cells for hantaviruses. To investigate the role of initial and innate immune response to hantaviruses we infected different cells with hantaviruses. We infected THP-1 (human monocyte line), primary human monocytes, 293HEK (human epithelial kidney line), MRC-5 (fetal lung fibroblasts cell line) and human vein endothelial cells (HUVEC) with Hantaan (HTNV), Sin Nombre (SNV) or Andes (ANDV) viruses. Culture supernatants were collected and assayed by ELISA for the presence mostly of proinflammatory cytokines/chemokines. Total celleularRNA was assayed for the presence of mRNA of cytokine/chemokine receptors and tumor necrosis factor (TNF) superfamily members using a multi-probe RNAse protection assay. TUNEL assay in conjuction to transmission electron microscopy was used to confirm apoptosis in infected 293HEK cells. Two-color immunofluoresence flow cytometry and IFA were performed to analyze morphological changes of infected monocytes/macrophages. Both, HFRS and HPS viruses induced production of several cytokines/chemokines in infected cells. HTNV seemed to be the main inductor for RANTES in the infected cell lines. The mRNA expression of chemokine receptors CCR1 and CCR5 were 4.8 and 12.6 folds higher in primary monocytes infected with HTV, than in control cells. However, substantial differences were found between primary monocytes and THP-1 cells. Infected macrophages underwent morphological changes toward dendritic-like cells and increased expression of co-stimulatory molecules: CD40, CD80, CD83 and CD86 were detected by IFA. HTNV was also the main GM-CSF inductor in MRC-5 cells. We found different cytokine/chemokine profile in 293HEK cells infected with HTNV in comparison with HPS viruses. Could it have some influence on kidney immunopathology is still under the question. Additionally, it was observed that hantaviruses cause CPE in 293HEK cells by apoptosis. The eludication of the pathways involved in innate immunity and factors controlling the transition to adaptive immunity will improve our understanding of the host response to hantaviruses.

hantaviruses; HFRS; HPS; cytokines; chemokines; dendritic cells; apoptosis

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